Deck 26: Special Topics 1 Epigenetics

Question 1

Imprinting disorders do not involve changes in DNA sequence, but only the methylated state of the DNA. Does it seem likely that imprinting disorders could be treated by controlling the maternal environment in some way, perhaps by dietary changes?

Answer 1

Imprinting of genes is an epigenetically regulated process in which the expression of gene will originate either from the maternal allele or paternal allele. If the allele of the mother is imprinted, the expression of gene will be of a paternal origin and only the allele from the father is going to be expressed and vice versa.
Imprinting disorders are the outcome of any epigenetic changes caused in maternal or paternal genes, i.e., in either egg or in sperm. The mutations caused in the imprinted genes are called epimutations and can arise by dysfunctional epigenetic changes or changes in the DNA sequence.
Most of the human disorders which are caused by dysfunctional imprinting originate during fetal growth and development. Because the imprinted genes act so early in the life of an individual, external or internal factors that can have serious phenotypic consequences due to epigenetic disturbances should be treated early to reduce such effects.
If we talk about cytoplasmic inheritance or about the epigenetic changes in egg, then yes the maternal environment does help in regulating the epigenetic disorders. Many factors could cause an imprinting disorder like pollution and abnormal diet in normal people. Various studies are being conducted that show epigenetic disorders like the imprinting disorders could be treated by controlling the maternal environment by means of a good diet, exercise. In one such study, pre-natal nutritional status influenced murine epigenetic regulation of the gene Igf2 , a gene which has been implicated in the development of a number of human cancers.
Another study gives evidence of miRNA presence in blood of people who eat wheat, potato, rice and cabbage. These miRNA interfere with the normal genes. So to some extent the changes made in diet and food habit of mother could help avoiding these diseases.
However, there are certain imprinting disorders which are linked to the paternal allele such as the Prader-Willi syndrome. In such imprinting disorders, treatment by controlling the maternal environment is not going to be very effective.

Question 2

What are the major mechanisms of epigenetic genome modification?

Answer 2

The RNA (ribonucleic acid) are the set of ribonucleic acid molecules that help in the translation of the proteins. They help in the formation of a particular amino acid with respect to the codon present in the DNA (deoxyribonucleic acid) sequence. The RNA is divided in three types: messenger RNA, ribosomal RNA and transfer RNA.
The central dogma concept suggests that the information in a living body is stored in form of protein. The DNA maintain the resource of the i9nformation, which can be encoded at a particular time. The DNA decoded is mainly done by the cumulative and sequential action of the three types of RNAs.
The messenger RNA or mRNA carries amino acid blueprint from the DNA of the cell to the ribosomes. The ribosomes perform the function of protein synthesis. The transfer RNA or tRNA carries the corresponding amino acids to the ribosomes for the formation of the new protein. The RNA themselves are consist of ribosomal RNA or rRNA molecules.

Question 3

Should fertility clinics be required by law to disclose that some assisted reproductive technologies (ARTs) can result in epigenetic diseases? How would you and your partner balance the risks of ART with the desire to have a child?

Answer 3

ART is defined as the fertility treatments in which both egg and sperm are manipulated in the laboratory. Recent observations of various studies have suggested a link between epigenetic errors and assisted reproductive technologies. Two of the most serious diseases born by Imprinting are Angelman Syndrome and Beckwith-Weidemann Syndrome which have been suggested to be associated with assisted reproductive technology and invitro fertilization.
BWS is classified as an overgrowth syndrome in which the children become abnormally large than normal and continues this growing state later in life too. Chromosome 11 is activated in both the parents whereas a normal cell has only one inactivated gene which do not express, either of maternal or paternal inheritance.
Angelman syndrome primarily affects the nervous system of the newly born baby. Main characteristic features of Angelman syndrome result from the loss of function of a gene UBE3A. Also most cases of Angelman syndrome are not inherited, particularly those caused by a deletion in the maternal chromosome 15 or by paternal uniparental disomy.
Fertility clinics should absolutely make their patients aware of the fact that some IVF and ART have a higher risk of imprinting syndrome than normal. Though the technique is like a boon for the couples who have infertility problems and couldn't reproduce, but reproducing to give birth to a child with an Epigenetic Imprinting disorder is even more painful and challenging.
The first and perhaps the strongest affirmation for imprinting disorder due to IVF treatment was the prevalence of large offspring syndrome in calves born through this technique. Thus, we know that indeed IVF and ART could give rise to Epigenetic diseases and this information must be fully and publicly disclosed so that all the factors can be assessed.
To balance the risks associated with assisted reproductive technology, the most important step that the couple should absolutely perform is a Pre-Implantation Genetic Diagnosis. This is a must for the cases of IVF as it could greatly reduce the risk of passing on a genetic disorder to future children. Knowing about a genetic or epigenetic disorder prior to implantation could help in deciding for an early termination of the process. Pre Implantation genetic diagnosis is the genetic profiling of embryos before implantation. Even oocyte and sperm could be genetically read using this technique before fertilization. Factors such as methionine content can also be assessed to check if any epigenetic errors are present in the parents.

Question 4

What parts of the genome are reversibly methylated? How does this affect gene expression?

Question 5

How can the role of epigenetics in cancer be reconciled with the idea that cancer is caused by the accumulation of mutations in tumor-suppressor genes and proto-oncogenes?

Question 6

What are the roles of proteins in histone modification?

Question 7

Would the knowledge that plant miRNAs can affect gene expression in your body affect your food choices?

Question 8

Describe how reversible chemical changes to histones are linked to chromatin modification.

Question 9

What is the histone code?

Question 10

What is the difference between silencing genes by imprinting and silencing by epigenetic modifications?

Question 11

Why are changes in nucleosome spacing important in changing gene expression?

Question 12

How do microRNAs regulate epigenetic mechanisms during development?

Question 13

What is the role of imprinting in human genetic disorders?